The UW ACE theme centers on a comprehensive developmental model of risk, risk processes, symptom emergence, and adaptation in autism spectrum disorder (ASD). According to this model, early autism risk factors (genetic/familial, brain, and environmental) lead to risk processes, namely, altered patterns of interaction between the child and his/her environment, which contribute to the abnormal development of neural circuitry and atypical behaviors. Project I seeks to identify autism risk genes through quantitative trait locus analysis, and also seeks to expand the set of component traits (endophenotypes) for which there is evidence for a genetic basis. In a sample of infant siblings of children with autism ("infant sibs"), Project II will investigate whether neurophysiological risk indices measured at 6-7 mos of age will improve our ability to identify infants who will develop ASD by age 2 years. This project also will investigate the efficacy of an early intervention that is designed to enhance early social responsiveness and communication for reducing autism symptoms in infant sibs by age 2 years. Project III will examine the predictive validity of measures of early prelinguistic abilities as risk indices for language impairment and ASD in infant sibs, and determine whether early intervention can influence the development of speech perception, speech preferences, and acquisition of speech in such at-risk infants. Project IV will identify early manifestations of abnormal brain development in 12-month old infant sibs using magnetic resonance imaging (MRI) and magnetic resonance spectroscopic imaging (MRSI), and examine relationships between these brain measures and clinical course and symptom onset. This project also will conduct brain imaging studies on adolescents with ASD who have been previously imaged by our group at age 3-4, 6-7, and 9-10 years to identify brain developmental changes that may be related to onset of seizures and behavioral decline during adolescence. Project V will conduct a prospective longitudinal cohort study of children with ASD who are transitioning into adolescence to investigate the role of genetic, child phenotypic, and family risk and protective factors in development of associated symptoms, such as depressive and anxiety symptoms. In a younger longitudinal cohort, this project also will conduct a follow-up study of a randomized, controlled trial of early intensive behavioral intervention to examine the long term effects on both core and associated symptoms. The proposed studies bring together strong expertise by UW investigators in early intervention, infant social cognition and prelinguistic development, child clinical and developmental psychology, child psychiatry, developmental cognitive neuroscience and neurophysiology, magnetic resonance imaging and spectroscopy, and quantitative approaches to genetic research. This combined expertise has allowed us to design projects aimed at discovering both etiologic pathways and effective treatments for autism spectrum disorder.